Physicians' Academy for Cardiovascular Education

Ambiguous association between NYHA class and CV outcomes in patients with HF

Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial

Literature - Rohde LE, Zimmerman A, Vaduganathan M, et al. - JAMA Cardiol. 2022, doi:10.1001/jamacardio.2022.4427

Introduction and methods


The NYHA classification system places patients with HF in one of four categories according to their degree of symptoms and limitations during physical activity. However, this widely used NYHA classification system is subject to limitations. For instance, it poorly correlates with cardiopulmonary exercise tests, and therefore fails to discriminate subgroups of HF patients across the spectrum of functional impairment [1-3]. Substantial overlap in objective measures exists, in particular for those classified as NYHA I and II. Consequently, patients with mild HF may be misclassified, i.e., classified in NYHA class I instead of NYHA class II, and be ineligible for therapies. Furthermore, changes in physician-assigned NYHA class may have low prognostic value [4].

Aim of the study

The aim of this study was to assess: (1) within-patient variation in NYHA class over 12 months after randomization; (2) the association between NYHA class and an objective measure of HF severity, such as NT-proBNP; and (3) their association with long-term prognosis. For these analyses, data from the PARADIGM-HF trial were used.


The PARADIGM-HF trial was a multicenter, double-blind, randomized clinical trial in which 8399 patients with chronic HF, LVEF ≤40%, and elevated levels of BNP or NT-proBNP were randomly assigned to either sacubitril/valsartan, 200 mg twice daily, or enalapril, 10 mg twice daily.

This secondary analysis compared data of 8326 patients classified as NYHA I to III at randomization Of these, 389 were classified as NYHA class I, 5919 were classified as NYHA class II, and 2018 were classified as NYHA class III.


Primary outcome was CV death or first HF hospitalization.

Main results

NYHA class variation in year 1

Association between objective measures and NYHA class

Prognostic value of NYHA class

Variation of NYHA class and outcomes


This study shows that the association between NYHA classification and cardiovascular outcomes among patients with HF is ambiguous. Higher NYHA classification is associated with worse prognosis. NYHA class I patients with high NT-proBNP levels manifested higher event rates than patients with lower NT-proBNP levels from any class. The authors concluded that NYHA classification as the main criterion to select treatment should be questioned as NYHA class alone fails to accurately differentiate mild forms of HF.


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Find this article online at JAMA Cardiology

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